Tetraspanin 1 inhibits TNFα-induced apoptosis via NF-κB signaling pathway in alveolar epithelial cells.

OBJECTIVE:Tetraspanin family plays an important role in the pathogenesis of cancer, but its role in lung fibrosis is unknown. To determine whether tetraspanin 1 a member of the family, may be involved in the pathogenesis of pulmonary fibrosis. METHODS:TNFα -stimulated human alveolar epithelial (A549) and alveolar epithelial type II cell (AT2) were treated in vitro. Murine pulmonary fibrosis model was generated by injection of bleomycin (BLM). The expression of was examined in vivo using the bleomycin-induced lung fibrosis model and tissue sample of IPF patients. Then we transfected the cells with Tduanyu1842N1 siRNA or plasmid and detected the expression changes of related proteins and cell apoptosis. RESULTS:In our study, we found that Tduanyu1842N1 was markedly down-regulated in lung tissue of patients with idiopathic pulmonary fibrosis (IPF) and in bleomycin-induced pulmonary fibrosis in mice. We also found that Tduanyu1842N1 was significantly down-regulated in A549 and primary (AT2) cells following exposure to TNFα. Meanwhile, Tduanyu1842N1 inhibited p-IκBα, which attenuated nuclear NF-κB translocation and activation and inhibited apoptosis. We demonstrated that Tduanyu1842N1 reduced Bax translocation and caspase-3 activation, inhibited the apoptosis by regulating the NF-κB pathway in response to TNFα. CONCLUSIONS:We conclude that Tduanyu1842N1 mediated apoptosis resistance of alveolar epithelial cells by regulating the NF-κB pathway. Tduanyu1842N1 may be a potential therapeutic target for pulmonary fibrosis or acute lung injury.

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